Plant Phenolics as Antibiotic Resistance Modifying Agents

There has recently been renewed interest in plant phenolics, long considered to be toxic and non-specific in their activity. Many activities have been reported for phenolic plant compounds, and of particular interest is their activity as antibiotic resistance modifying agents against Gram-positive bacteria and mycobacteria. Multidrug-resistance (MDR) exhibited by many bacterial species is a major problem in treating both hospital and community acquired infections. A modifying agent is a compound which reduces the minimum inhibitory concentration (MIC) for an antibiotic. This could be of great benefit in combinatory therapy, perhaps facilitating the reintroduction of antibiotics that are no longer effective due to resistance. An example in clinical use is Unasyn™ comprising the β-lactamase inhibitor sulbactam in combination with ampicillin. Polyphenols from green tea, epicatechin gallate [1] and epigallocatechin gallate have been shown to potentiate oxacillin activity against methicillin-resistant Staphylococcus aureus (MRSA) [1] and to have modest activity in reducing the MIC of some standard antibiotics against effluxing strains of S. aureus [2]. Resistance modifying activity has also been reported for the phenolic abietanes, totarol and ferruginol [2] isolated from conifer species [3; 4], for carnosic acid from Rosmarinus officinalis L. [5], and anacardic acid from the cashew Anacardium occidentale L. [6]. Small differences in structure such as the position of a hydroxyl group can have a considerable effect on modulatory activity [3; 4] which suggests a more subtle mode of action for these phenolics than general membrane perturbation. Recent reports have indicated a potentially useful separation between the concentrations required for biological activity and cytotoxicity for both ferruginol and totarol [7].

Acknowledgements: We thank Stiefel International R & D Ltd for funding this study.

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